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Author Kreiner, E.; Waage, J.; Standl, M.; Brix, S.; Pers, T.H.; Couto Alves, A.; Warrington, N.M.; Tiesler, C.M.T.; Fuertes, E.; Franke, L.; Hirschhorn, J.N.; James, A.; Simpson, A.; Tung, J.Y.; Koppelman, G.H.; Postma, D.S.; Pennell, C.E.; Jarvelin, M.-R.; Custovic, A.; Timpson, N.; Ferreira, M.A.; Strachan, D.P.; Henderson, J.; Hinds, D.; Bisgaard, H.; Bonnelykke, K. url  doi
  Title Shared genetic variants suggest common pathways in allergy and autoimmune diseases Type Journal Article
  Year (down) 2017 Publication The Journal of Allergy and Clinical Immunology Abbreviated Journal J Allergy Clin Immunol  
  Volume Issue Pages  
  Keywords Allergy; autoimmune disease; autoimmunity; genetic association studies; single nucleotide polymorphism  
  Abstract BACKGROUND: The relationship between allergy and autoimmune disorders is complex and poorly understood. OBJECTIVE: We sought to investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. METHODS: We meta-analyzed 2 genome-wide association studies on self-reported allergy and sensitization comprising a total of 62,330 subjects. These results were used to calculate enrichment for single nucleotide polymorphisms (SNPs) previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites and characterized commonalities in variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DNase-hypersensitive site data. Finally, we compared the allergy data with those of all known diseases. RESULTS: Among 290 loci previously associated with 16 autoimmune diseases, we found a significant enrichment of loci also associated with allergy (P = 1.4e-17) encompassing 29 loci at a false discovery rate of less than 0.05. Such enrichment seemed to be a general characteristic for autoimmune diseases. Among the common loci, 48% had the same direction of effect for allergy and autoimmune diseases. Additionally, we observed an enrichment of allergy SNPs falling within immune pathways and regions of chromatin accessible in immune cells that was also represented in patients with autoimmune diseases but not those with other diseases. CONCLUSION: We identified shared susceptibility loci and commonalities in pathways between allergy and autoimmune diseases, suggesting shared disease mechanisms. Further studies of these shared genetic mechanisms might help in understanding the complex relationship between these diseases, including the parallel increase in disease prevalence.  
  Address COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark  
  Corporate Author Thesis  
  Impact Factor 11,476 First Author Kreiner E Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Bønnelykke K  
  ISSN 0091-6749 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28188724 Approved no  
  Call Number Serial 346  
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